The long-term objective of this project is to develop a novel blood storage system that will extend the shelf life of additive system red cell units, and at the same time, deliver red cells of higher efficacy and lower toxicity for transfusion therapy. In this system, red cells are stored in a modified additive solution under oxygen-depleted condition (anaerobic storage). The final product will have extended shelf life (9 weeks or more) as well as higher efficacy and lower toxicity compared to same-aged blood stored by conventional methods (more viable cells, higher oxygen delivery capacity immediately after transfusion and more deformable cells for better capillary perfusion). The new storage system is design to be readily accommodated by the current blood banking operation without incurring major alteration in procedures or equipments. In the Phase I of this project, an experimental procedure was used to demonstrated that anaerobic storage yields;i) a significantly higher post- transfusion recovery compared to the conventional method after 6 weeks of storage;and ii) a comparable 9-week recovery compared to 6-week storage under conventional conditions. The main aim of this Phase II proposal is to demonstrate that an experimental hardware/ processes used in the Phase I can be reduced to practice by fabricating a blood collection/storage system that is self-contained and easily accommodated under current blood bank settings without compromises in its performances. In partnership with University of Pittsburgh, Filtertek and Multisorb Technologies, several prototypes storage system will be designed, fabricated and tested in vitro. Subsequently, an optimized prototype system will be tested in a clinical trial at Dartmouth- Hitchcock Medical Center with a goal of obtaining results comparable to ones attained under experimental procedure in the Phase I. PUBLIC HEALTH RELEVANCE: In the past several years, a number of papers have appeared in scientific journals questioning the quality of red blood cells stored for transfusion. They indicated that;i) worse clinical outcomes were associated with higher number of units transfused;ii) blood transfusion may not have induced increased oxygen utilization in tissues;and iii) worse post-operative outcomes were associated with patients receiving blood stored for longer than 14 days compared with patients receiving less than 14-day old blood. Proposed anaerobic red blood cell storage system delivers higher post- transfusion viability and uncompromised oxygen delivery capacity, thereby improving the efficacy of transfusion therapy while reducing side effects of transfusion. Transfusion of such red cells will reduce the frequency- and time- averaged blood transfusion volume and total iron burden in subjects who require chronic transfusion (e.g., sickle cell disease or beta-thalassemia). Extended shelf life will improve the logistics of general blood bank operations, alleviate the periodic blood shortages, and increase the utility of pre-operative autologous blood donation.